Graft with expandable region and methods of making and using the same

ABSTRACT

A vascular graft suitable for implantation, and more particular to a vascular graft having an expandable outflow region for restoring patency of the graft after implantation into a body lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to U.S. ProvisionalPatent Application No. 61/857,181, filed Jul. 22, 2013, the contents ofwhich are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention and disclosure relates to various embodiments ofvascular grafts suitable for implantation, including the manufacturingand use of such grafts. In certain embodiments of the presentdisclosure, one or more expandable first regions are provided forrestoring patency of the graft after implantation into a body lumen.

BACKGROUND OF THE INVENTION

Vascular diseases are prevalent worldwide. Bypass surgery, whereby aconduit, either artificial or autologous, is grafted into an existingvessel to circumvent a diseased portion of the vessel or to restoreblood flow around a blocked or damaged blood vessel, is one of the mostcommon treatments for such diseases.

Vascular grafts are also used as entry sites in dialysis patients. Thegraft connects or bridges an artery to a vein in the patient's body. Aneedle is inserted into the graft, allowing for blood to be withdrawnand passed through a hemodialysis machine and returned to the patientthrough a second needle inserted into the graft.

A significant number of by-pass grafts fail within 5 to 7 years. Theaverage life-span for hemodialysis grafts is even shorter, often lessthan two years. A primary cause of graft failure is the closing of thegraft due to tissue in-growth and eventually thrombosis formation. Thesmaller the graft diameter, the higher the graft failure rate. The lostpatency resulting from graft closure or collapse is particularlyproblematic at the outflow site where the outflow end of the grafttouches the vessel.

However, this issue has not been adequately addressed by conventionaltechniques to restore patency, which typically include surgicalprocedures (e.g., thrombectomy or percutaneous thrombectomy) or chemicalintervention techniques (e.g., administration of anti-clotting oranti-platelet drugs, such as ticlopidine, aspirin, dipyridimole, orclopidogrel) to remove ingrown tissue or clotting that otherwisecontributes to graft failure. In particular, surgical and chemicalinterventions can introduce unnecessary risk (e.g., of infection,bleeding, etc.) and often are inadequately effective to maintain patencyover longer periods of time.

Thus, there is a need for a graft for which patency can be restoredeasily after implantation without requiring risky and ineffectivechemical or surgical interventions. There is also a need for differentgraft structures that utilize various features of the graft technologiesdisclosed herein.

SUMMARY

There is a need for a vascular graft having an expandable outflow regionwhich enables patency to be restored easily after implantation withoutrequiring risky and ineffective chemical or surgical interventions.Embodiments of the present disclosure and invention are directed towardfurther solutions to address the aforementioned needs, in addition tohaving other desirable characteristics.

In accordance with an embodiment of the present invention, a graft isprovided. The graft includes a conduit having a wall. The conduitincludes at least one inflow aperture at an inflow end of a body region,and an outflow aperture at an outflow end of an outflow region oppositefrom the at least one inflow aperture. The wall includes a supportstructure and a biocompatible layer. The support structure along theoutflow region is under continuous compressive stress resulting from acontinuous applied load caused by the biocompatible layer against thesupport structure.

In accordance with aspects of the present invention, the compressivestress resulting from the continuous applied load in the outflow regionis greater than a compressive stress resulting from a continuous appliedload in the body region. In accordance with aspects of the presentinvention, the compressive stress experienced by the support structureresulting from the continuous applied load in the outflow region isincrementally greater at each segment along the support structure thatis incrementally more distal from the at least one inflow aperture. Thecompressive stress experienced by the support structure resulting fromthe continuous applied load in the outflow region causes an elasticdeformation of the support structure in the outflow region. Inaccordance with aspects of the present invention, the elasticdeformation of the support structure in the outflow region isincrementally greater at each segment along the support structure thatis incrementally more distal from the at least one inflow aperture. Theelastic deformation of the support structure in the outflow region isreversible. The compressive stress resulting from the continuous appliedload in the body region does not elastically deform the supportstructure in the body region.

In accordance with aspects of the present invention, the supportstructure prior to combination with the biocompatible layer to form thewall has multiple effective outer diameter measurements, and the supportstructure after combination with the biocompatible layer to form thewall has a generally uniform effective outer diameter measurement. Themultiple effective outer diameter measurement along the body region canbe a constant effective outer diameter measurement. The multipleeffective outer diameter measurement along the outflow region can be aneffective outer diameter measurement that is incrementally greater ateach segment along the support structure that is incrementally moredistal from the at least one inflow aperture. The generally uniformeffective outer diameter measurement can be a constant effective outerdiameter measurement along the body region, and a constrained effectiveouter diameter measurement along the outflow region. The constrainedeffective outer diameter measurement is approximately equal to theconstant effective outer diameter measurement. The compressive stressresulting from the continuous applied load maintains the supportstructure along the outflow region at the constrained effective outerdiameter measurement.

In accordance with aspects of the present invention, a counter forcecomprising a radial expansion force applied to the support structurealong the outflow region causes plastic deformation of the biocompatiblelayer. The counter force comprising a radial expansion force applied tothe support structure in the outflow region causes a reduction of thecompressive stress experienced by the support structure. Followingapplication of a counter force comprising a radial expansion forceapplied to the support structure in the outflow region, the graftreconfigures in such a way as to result in a plastically deformedbiocompatible layer and a compressive stress experienced by the supportstructure that is less than the compressive stress experienced by thesupport structure prior to application of the counter force. Followingapplication of a counter force comprising a radial expansion forceapplied to the support structure in the outflow region, the graftreconfigures in such a way as to result in a plastically deformedbiocompatible layer. Following application of a counter force comprisinga radial expansion force applied to the support structure in the outflowregion, the graft reconfigures in such a way as to result in the supportstructure experiencing residual compressive stress where there waspreviously continuous compressive stress experienced by the supportstructure prior to application of the counter force.

In accordance with aspects of the present invention, a counter forcecomprising a radial expansion force applied to the support structure inthe outflow region reconfigures the support structure along the outflowregion from the constrained effective outer diameter measurement to anexpanded effective outer diameter measurement that is greater than theconstrained effective outer diameter measurement along at least aportion of the support structure in the outflow region. In accordancewith aspects of the present invention, the expanded effective outerdiameter measurement is at least 1 mm greater than the constrainedeffective outer diameter measurement along at least a portion of thesupport structure in the outflow region. In accordance with aspects ofthe present invention, the expanded effective outer diameter measurementof the support structure along the outflow region after beingreconfigured is at least 1 mm greater than the constrained effectiveouter diameter measurement along the entire portion of the supportstructure in the outflow region.

In accordance with further aspects of the present invention, conduit caninclude a second inflow aperture. The longitudinal axis of the secondinflow aperture intersects a longitudinal axis of the at least oneinflow aperture at a non-parallel angle. In accordance with aspects ofthe present invention, the non-parallel angle comprises an angle betweenabout 25° and 45°. In accordance with one aspect of the presentinvention, the non-parallel angle is about 35°.

In accordance with aspects of the present invention, the supportstructure is constructed of a shape memory alloy. In accordance with oneaspect of the present invention, the support structure is constructed ofnitinol. The support structure can have a zigzag wire shape.

In accordance with aspects of the present invention, the biocompatiblelayer comprises an expandable polymer. The biocompatible layer caninclude ePTFE. The biocompatible can include a biocompatible outerlayer. The biocompatible layer can include a biocompatible inner layer.The biocompatible outer layer and the biocompatible inner layerencapsulate the support structure. In accordance with one aspect of thepresent invention, the biocompatible layer is not a surface modifyingcoating.

In accordance with one example embodiment, a vascular graft is provided.The vascular graft includes a conduit having a wall. The wall includesat least one inflow aperture at an inflow end of a body region, and anoutflow aperture at an outflow end of an outflow region opposite fromthe at least one inflow aperture. The wall includes a support structureand a biocompatible layer. Prior to combination with the biocompatiblelayer to form the wall, the support structure includes multipleeffective outer diameter measurements along its length. The multipleeffective outer diameter measurements include a constant effective outerdiameter measurement along the body region, and an effective outerdiameter measurement along the outflow region that is incrementallygreater at each segment along the support structure that isincrementally more distal from the at least one inflow aperture. Aftercombination with the biocompatible layer to form the wall, the supportstructure in the outflow region is under continuous compressive stressresulting from a continuous applied load caused by the biocompatiblelayer which maintains the support structure along the outflow region ata constrained effective outer diameter measurement that is notincrementally greater at each segment along the support structure thatis incrementally more distal from the at least one inflow aperture.After application of a counter force to the support structure in theoutflow region the support structure in the outflow region isreconfigured from the constrained effective outer diameter measurementto an expanded effective outer diameter measurement, at least a portionof which is at least one millimeter greater than the constrainedeffective outer diameter measurement.

In accordance with an example embodiment of the present invention, amethod of expanding an outflow end of an implanted graft is provided.The method includes (a) identifying an implanted graft and (b) andapplying a counterforce. The vascular graft includes a conduit having awall. The conduit includes at least one inflow aperture at an inflow endof a body region, and an outflow aperture at the outflow end of anoutflow region opposite from the at least one inflow aperture. The wallincludes a support structure and a biocompatible layer. Prior tocombination with the biocompatible layer to form the wall, the supportstructure comprises multiple effective outer diameter measurementscomprising a constant effective outer diameter measurement along thebody region and an effective outer diameter measurement along theoutflow region that is incrementally greater at each segment along thesupport structure that is incrementally more distal from the at leastone inflow aperture. After combination with the biocompatible layer toform the wall, the support structure in the outflow region is undercontinuous compressive stress resulting from a continuous applied loadcaused by the biocompatible layer which maintains the support structurein the outflow region at a constrained effective outer diametermeasurement that is not incrementally greater at each segment along thesupport structure that is incrementally more distal from the at leastone inflow aperture. Application of the counter force to the supportstructure in the outflow region reconfigures the support structure alongthe outflow region from the constrained effective outer diametermeasurement to an expanded effective outer diameter measurement that isgreater than the constrained effective outer diameter measurement,thereby expanding the outflow region of the implanted graft.

In accordance with aspects of the present invention, the outflow regioncomprises an outflow end that has collapsed, stenosed, or has sustainedintimal hyperplasia. The outflow end that has collapsed, stenosed, orhas sustained intimal hyperplasia end impairs patency of a vessel inwhich the graft is implanted.

In accordance with aspects of the present invention, applying thecounter force comprises expanding an expandable device in the outflowregion of the implanted graft. Prior to expanding the expandable devicethe expandable device is advanced to the outflow region. Prior toadvancing the expandable device to the outflow region, the expandabledevice is introduced into the implanted graft percutaneously.

In accordance with aspects of the present invention, the expandedeffective outer diameter measurement is at least one millimeter greaterthan the constrained effective outer diameter measurement. In accordancewith aspects of the present invention, the expanded effective outerdiameter measurement is at least one millimeter greater than theconstrained effective outer diameter measurement along any portion ofthe support structure in the outflow region.

In accordance with one example embodiment, a method of expanding anoutflow region of an implanted graft is provided. The method includes(a) providing an implanted graft having an expandable outflow region,and (b) applying a counter force to the outflow region. The implantedgraft includes a conduit having a wall. The conduit includes at leastone inflow aperture at an inflow end of a body region, and an outflowaperture at the outflow end of an outflow region opposite from the atleast one inflow aperture. The wall includes a support structure and abiocompatible layer. The support structure in the outflow region isunder compressive stress resulting from an applied load caused by thebiocompatible layer. Applying a counter force to the support structurein the outflow region reconfiguring the support structure along theoutflow region from a constrained effective outer diameter measurementto an expanded effective outer diameter measurement that is greater thanthe constrained effective outer diameter measurement, thereby expandingthe outflow end of the implanted graft.

In accordance with one example embodiment of the present invention, amethod of making a graft having an expandable outflow end is provided.The method includes (a) providing a support structure having at leastone inflow aperture at an inflow end of a body region and an outflowaperture at an outflow end of an outflow region opposite from the atleast one inflow aperture. The support structure has multiple effectiveouter diameter measurements comprising a constant effective outerdiameter measurement along the body region of the support structure andan incrementally increasing effective outer diameter measurement alongthe outflow region of the support structure. The method further includes(b) combining the support structure with at least one biocompatiblelayer to form a wall comprising the support structure and the at leastone biocompatible layer. The method further includes (c) inserting amandrel into the outflow aperture proximal to the outflow end of thesupport structure. The method further includes (d) constraining theincrementally increasing effective outer diameter measurement proximalto the outflow region of the support structure with a compression wrapin such a way that a continuous compressive stress results from acontinuous applied load caused by the biocompatible layer whichmaintains the support structure along the outflow region in aconstrained effective outer diameter measurement that is uniform withthe constant effective outer diameter measurement. The method furtherincludes (e) sintering the at least one biocompatible layer at a segmentin the outflow region.

BRIEF DESCRIPTION OF THE FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawings will be provided by the Office upon request and paymentof the necessary fee.

These and other characteristics of the present invention will be morefully understood by reference to the following detailed description inconjunction with the attached drawings, in which:

FIG. 1A is a schematic view of a vascular graft according to anembodiment of the present invention;

FIG. 1B is a schematic view of a vascular graft according to anotherembodiment of the present invention;

FIG. 2A is a side view of an embodiment of a support structure of thevascular graft shown in FIG. 1A, illustrating the support structureprior to combination with a biocompatible layer, according to one aspectof the present invention;

FIG. 2B is a schematic view of an embodiment of the vascular graft shownin FIG. 1A after combining the support structure shown in FIG. 2A withthe biocompatible layer, according to one aspect of the presentinvention;

FIG. 2C is a schematic view of an embodiment of the vascular graft shownin FIG. 1A after expanding the outflow region of the support structureof the vascular graft shown in FIG. 2B, according to one aspect of thepresent invention;

FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, and 3O arewireframe views showing various embodiments of the “flared” outflowregion of the support structure, according to aspects of the presentinvention;

FIG. 4A is a schematic cross-sectional view of a support structure takenthrough line 68 of FIG. 4B;

FIG. 4B is a schematic view of an embodiment of the support structureuseful to construct the region proximal to the first region of avascular graft shown in FIGS. 1A and 1B, according to one aspect of thepresent invention;

FIG. 5A is a cross-sectional view of a vascular graft similar to the oneshown in FIG. 1A taken through sectional line 5-5 of FIG. 1A;

FIG. 5B is a detail view taken about the border 82 of FIG. 5A, accordingto one aspect of the present invention;

FIG. 5C is a cross-sectional view of a vascular graft similar to the oneshown in FIG. 1A taken through sectional line 5-5 of FIG. 1A, accordingto one aspect of the present invention;

FIG. 5D is cross-sectional view of a vascular graft similar to the oneshown in FIG. 1A taken through sectional line 5-5 of FIG. 1A, accordingto one aspect of the present invention;

FIG. 6A is a side view of an embodiment of a support structure of thevascular graft shown in FIG. 1B, illustrating the support structureprior to combination with the biocompatible layer, according to oneaspect of the present invention;

FIG. 6B is a schematic view of an embodiment of the vascular graft shownin FIG. 1B after combining the support structure shown in FIG. 6A withthe biocompatible layer, according to one aspect of the presentinvention;

FIG. 6C is a schematic view of an embodiment of the vascular graft shownin FIG. 1B after expanding the outflow region of the support structureof the vascular graft shown in FIG. 6B, according to one aspect of thepresent invention;

FIG. 7A is a top view of an embodiment of a support structure of thevascular graft shown in FIG. 1B;

FIG. 7B is a top wireframe view of the support structure of the vasculargraft shown in FIG. 7A;

FIG. 7C is a side wireframe view of the support structure of thevascular graft shown in FIG. 7B;

FIG. 8A is a side view of an embodiment of a support structure similarto the vascular graft shown in FIG. 1A, illustrating the supportstructure prior to combination with the biocompatible layer, accordingto one aspect of the present invention;

FIG. 8B is a schematic view of an embodiment of the vascular graft shownin FIG. 8A after combining the support structure shown in FIG. 8A withthe biocompatible layer, according to one aspect of the presentinvention;

FIG. 8C is a schematic view of an embodiment of the vascular graft shownin FIG. 8B after expanding the outflow region of the support structureshown in FIG. 8B, according to one aspect of the present invention;

FIG. 8D is side wireframe view of the support structure shown in FIG.8C, according to one aspect of the present invention;

FIG. 8E is a photograph of the embodiment of the support structure shownin FIGS. 8A through 8D, according to one aspect of the presentinvention;

FIG. 8F is a schematic view of an embodiment of the support structureproximal to the inflow region of a vascular graft shown in FIGS. 8A, 8Dand 8E, according to one aspect of the present invention;

FIG. 9A is a side view of an embodiment of a support structure of thevascular graft similar to the embodiment shown in FIG. 1B, illustratingthe support structure prior to combination with the biocompatible layer,according to one aspect of the present invention;

FIG. 9B is a schematic view of an embodiment of the vascular graft shownin FIG. 1B after combining the support structure shown in FIG. 9A withthe biocompatible layer, according to one aspect of the presentinvention;

FIG. 9C is a schematic view of an embodiment similar to the vasculargraft shown in FIG. 1B after expanding the outflow region of the supportstructure of the vascular graft shown in FIG. 9B, according to oneaspect of the present invention;

FIG. 9D is a photograph of the embodiment of the support structure shownin FIG. 9A, according to one aspect of the present invention;

FIG. 9E is a photograph of the embodiment of the vascular graft shown inFIG. 9B, according to one aspect of the present invention;

FIG. 9F is a photograph of the embodiment of the vascular graft shown inFIG. 9C with an extension lumen extending from the branch, according toone aspect of the present invention;

FIG. 9G is a photograph similar to FIG. 9F further illustrating a border84 encircling a portion of the graft at the branch, according to oneaspect of the present invention;

FIG. 9H is a schematic representative detail cross-sectional view of anembodiment of FIGS. 9B and 9C taken about border 84 of FIG. 9G,according to an aspect of the present invention;

FIG. 10A is a schematic illustration of an expandable device similar tothe embodiment of FIG. 9F, being used to expand the outflow region of avascular graft, according to one aspect of the present invention;

FIG. 10B is a detail view taken about border 86 of FIG. 10B, accordingto one aspect of the present invention;

FIG. 11 is a photograph demonstrating an expandable device being used toexpand the outflow region of a vascular graft, according to one aspectof the present invention;

FIG. 12 is a flow chart depicting a method of expanding an outflowregion of a vascular graft according to one aspect of the presentinvention;

FIG. 13 is a flow chart depicting a method of making a vascular graftaccording to one aspect of the present invention;

FIG. 14A is a photograph illustrating a step of a method of making avascular graft according to one aspect of the present invention;

FIG. 14B is a photograph illustrating a step of a method of making avascular graft according to one aspect of the present invention; and

FIG. 15A is a schematic view of a vascular graft according to anotherembodiment of the present invention illustrating the support structureprior to combination with a biocompatible layer, according to one aspectof the present invention;

FIG. 15B is a schematic view of an embodiment of the support structureof FIG. 15A after the biocompatible layer(s) has been added to thesupport structure, according to one aspect of the present invention;

FIG. 15C is a schematic view of an embodiment of the vascular graft ofFIG. 15B implanted into one or more vessels, according to one aspect ofthe present invention;

FIG. 16A is a schematic view of a vascular graft according to anotherembodiment of the present invention illustrating the support structureprior to combination with a biocompatible layer, according to one aspectof the present invention;

FIG. 16B is a schematic view of an embodiment of the support structureof FIG. 16A after the biocompatible layer(s) has been added to thesupport structure, according to one aspect of the present invention;

FIG. 16C is a schematic view of an embodiment of the vascular graft ofFIG. 16B implanted into one or more vessels, according to one aspect ofthe present invention;

FIG. 17A is a schematic view of a vascular graft according to anotherembodiment of the present invention illustrating the support structureprior to combination with a biocompatible layer, according to one aspectof the present invention;

FIG. 17B is a schematic view of an embodiment of the support structureof FIG. 17A after the biocompatible layer(s) has been added to thesupport structure, according to one aspect of the present invention; and

FIG. 17C is a schematic view of an embodiment of the vascular graft ofFIG. 17B implanted into one or more vessels, according to one aspect ofthe present invention.

DETAILED DESCRIPTION

The present invention is directed to various embodiments of a radialsupport graft device and/or stent-graft useful for various vascularaccess applications, including but not limited facilitating vascularaccess in vascular bypass applications, facilitating treatment ofatherosclerosis and facilitating arterial venous access for dialysistreatment. In an exemplary embodiment, the devices of the presentinvention have an expandable flared end, bifurcated design, and/or stent(i.e., radial support structure) pattern configured to facilitatevascular access and substantially sutureless and secure implantation ofthe device into the vasculature of a patient. Although the presentinvention will be described with reference to the figures, it should beunderstood that many alternative forms can embody the present invention.One of skill in the art will additionally appreciate different ways toalter the parameters disclosed, such as the size, shape, or type ofelements or materials, in a manner still in keeping with the spirit andscope of the present invention.

Referring now to the exemplary embodiments shown in FIGS. 1A through17C, wherein like parts are designated by like reference numeralsthroughout, these figures illustrate example embodiments of a vasculargraft, and methods of producing and using the same according to thepresent invention. In particular, these embodiments show a vasculargraft (e.g., for anastomosis) having an outflow region capable of beingexpanded, for example, after implantation into a body passageway (e.g.,a blood vessel) to restore patency, and methods for using and producingthe same.

A vascular graft 10, in accordance with an exemplary embodiment of thepresent invention, is illustrated in FIG. 1A. Vascular graft 10 isconfigured as a conduit 20 having a hollow body region 43 with aninternal lumen 21 formed by wall 30. The conduit 20 comprises at leastone inflow aperture 32 at an inflow end 35 and an outflow aperture 34 atan outflow end 36 of an outflow region 42 opposite from the at least oneinflow aperture 32. The inflow end 35 and outflow end 36, of the conduit20 are in fluid communication with each other via internal lumen 21,which is defined conduit 20 and extends between the at least one inflowaperture 32 and the outflow aperture 34. The wall 30 of conduit 20 isformed by a support structure 40 and a biocompatible layer 50. Supportstructure 40 may be any device configured to maintain patency of avessel. Exemplary support structures 40 may include stents. In oneembodiment support structure 40 may be an expandable structure andconstructed from a shape memory alloy, such as nitinol. In an exemplaryembodiment, a biocompatible layer 50, which may be configured as acover, sheath or sleeve, may at least partially or fully cover anexterior surface of support structure 40. The support structure 40 maybe separate from the biocompatible layer 50, adhered to thebiocompatible layer 50, at least partially embedded in the material ofthe biocompatible layer 50, or any permutation of the foregoing. Thesupport structure 40 along the outflow region 42 is under continuouscompressive stress (S) resulting from a continuous applied load causedby the biocompatible layer 50 against the support structure 40. Forexample, the support structure 40 may be arranged to springingly orresiliently exert a continuous radially outwardly directed force againstthe biocompatible layer 50, which biocompatible layer 50 correspondinglyexerts the continuous compressive stress on the support structure 40.

FIGS. 2A, 2B, and 2C show views of the support structure 40 of thevascular graft 10 shown in FIG. 1A, illustrating the support structure40 prior to combination with a biocompatible layer 50 to form wall 30(FIG. 2A), after combining the support structure 40 shown in FIG. 2Awith the biocompatible layer 50 to form wall 30 (FIG. 2B), and afterexpanding the outflow region 42 of the support structure 40 of thevascular graft 10 shown in FIG. 2B (FIG. 2C).

In FIG. 2A, the support structure 40 prior to combination with thebiocompatible layer 50 to form the wall 30 conduit 20 has varying outerdiameter along the length of support structure 40. As shown, supportstructure 40 has a constant effective outer diameter measurement D_(c)along the body region 43, and a radially and outwardly flaring effectiveouter diameter measurement D_(inc) that increases along at least aportion of the outflow region 42 towards outflow aperture 34 to give theoutflow region a “flared” shape or appearance, as discussed furtherbelow. This outwardly flared configuration of support structure 40allows for substantially sutureless attachment and retention of stentgraft 10 within the vasculature of a patient. Upon covering the supportstructure 40 with biocompatible layer 50, as show in FIG. 2A, the flaredoutflow region 42 is constricted such that conduit 20 is reshaped tohave a constant effective outer diameter measurement D_(c) along thelength of body region 43 and outflow region 42, as shown in FIG. 2B. Inan exemplary embodiment, outflow region 42 is constructed from ashape-memory alloy, such as a nitinol, that is capable of expanding fromits constrained state to achieve and maintain a flared configurationupon application of an expansion force, such as balloon catheterexpansion. This shape memory support structure 40 may be self-expanding,but is unable to assume its flared state without balloon expansion dueto the compressive stress applied by biocompatible layer 50. 2C showsthe expanded effective outer diameter measurement D_(exp) of the supportstructure 40 after an external expansion force is applied to the outflowregion 42 of the support structure 40 in FIG. 2B.

FIGS. 3A-3O, show various example embodiments of the outflow region 42of support structure 40, depicting various flared configurations. Theseillustrations represent the wireframe profile of the support structure40, without depiction its strut pattern. Those skilled in the art willappreciate that a number of different strut patterns can be utilized,and that all such patterns are considered as falling within the scope ofthe profiles depicted. With regards to FIGS. 3K-3O, those skilled in theart will additionally appreciate that the diameter of each supportstructure segment along the support structure 40 in the outflow region42 may be different, depending on the particular implementation. In theexample embodiment of FIGS. 3K and 3M, each of the support structuresegments is generally constructed from a single zigzag ring (asexplained below), such that the support structure segments form aconduit having stepwise increments that increase in diameter as theyapproach outflow aperture 34. In another example embodiment, supportstructure 40 may include a plurality of these stepwise increments at asufficiently frequent intervals such that a portion of outflow region42, i.e. the portion between a proximal and distal end of outflow region42, appear to have a substantially uniform linear change in diameter(e.g. FIG. 3A), or alternatively a curvilinear change in diameter (e.g.,FIGS. 3F and 3I), rather than a stepwise change in diameter. In yetanother example embodiment the increments can occur in such a way thatthe effective outer diameter does not change along at least one segmentalong the support structure 40 in the outflow region 42 (e.g., FIGS. 3B,3C, 3G, 3J, 3L, 3M, 3N, and 3O). In certain example embodiments theincrements can occur in such a way that combines any of theconfigurations above (e.g., FIGS. 3L, 3N). Those skilled in the art canreadily envision other suitable flared configurations that may beconsidered to fall within the scope of the present invention.

Turning now to FIG. 4, there is illustrated a wire frame design formingan exemplary support structure 40 construction at outflow region 42.FIG. 4 shows a properly scaled illustration of the support structure 40showing the precise relative proportions of the support structurepattern depicted therein in a flat orientation. As shown, the supportstructure 40 is constructed of a series of interconnected rings (e.g.,R₁, R_(n), R_(n+1), R_(n+2), R_(n+3), where n=an integer representing),each comprising a substantially zigzag shape comprising a series ofpeaks and valleys. Once the flattened wire frame is rolled into a threedimensional cylindrical configuration, the peaks or crowns of each ringdirectly faces and is aligned with a corresponding valley of anadjoining ring and vice versa. This peak to valley arrangement ispresent throughout the length of support structure 40 and creates aflexible structure, allowing stent 20 to bend and turn when implanted.FIG. 4 illustrates an exemplary strut or stent pattern of supportstructure 40.

In the example shown in FIG. 4, the support structure 40 in the outflowregion 42 has an effective outer diameter measurement D_(inc) that isincrementally greater at each segment (D, D₁, D₂, D₃) along the supportstructure 40 for each incrementally more distal portion or segmentsextending from the at least one inflow aperture 32 to the at least oneoutflow aperture 34. In this non-limiting example, the support structure40 can be constructed of a series of interconnected rings (e.g., R₁,R_(n), R_(n+1), R_(n+2), R_(n+3), where n=an integer representing), eachcomprising a substantially zigzag shape. By way of example, in oneembodiment, rings R₁ and R_(n) of the support structure 40 are locatedin the body region 43 proximal to the outflow region 42, whereas ringsR₃, R₄, and R₅ are located in the outflow region 42, with R₅ forming anedge of outflow aperture 34. Rings R₁ and R_(n) of body region 43 mayhave the same size and dimension D. Whereas the rings in the body region43 are generally have the same size and dimension, rings R₃, R₄, and R₅have incrementally increasing width of a ring (i.e. lengths of the peaksand valleys) D1, D2, and D3. The effective outer diameter measurement ofthe support structure 40 increases at each ring segment R as the widthof each ring segment D increases. For example, the width D1 of ringsegment R3 is greater than the width D of ring segment R_(n), therebyincreasing the effective outer diameter measurement of the supportstructure 40 at ring segment R₃ relative to ring segment R_(n), thewidth D₂ of ring segment R₄ is greater than the width D₁ of ring segmentR₃, thereby increasing the effective outer diameter measurement of thesupport structure 40 at ring segment R₄ relative to ring segment R₃, andthe width D₃ of ring segment R₅ is greater than the width D₂ of ringsegment R₄, thereby increasing the effective outer diameter measurementof the support structure 40 at ring segment R₅. The effective outerdiameter measurement of this embodiment of support structure 40 in theoutflow region 42 therefore is incrementally greater at each segmentalong the support structure 40 that is incrementally more distal formthe at least one inflow aperture 32. Although there is shown only 3 ringsegments R_(n+1), R_(n+2), and R_(n+3) with incrementally increasingdimensions D1, D2, and D3, respectively, it is to be understood that theoutflow region 42 of the support structure 40 can be provided with more(e.g., 4, 5, 6, etc.) or less (e.g., 2) ring segments R depending on theparticular application, as will be appreciated by those skilled in theart.

As shown in the embodiments illustrated in FIGS. 3A-3O (describedabove), any particular segment R (R_(n+1), R_(n+2), R_(n+3)) havingwidth D (D₁, D₂, D₃) can be provided with a constant effective outerdiameter measurement D_(c). In such embodiments, the support structure40 flares at each location in the outflow region 42 in which theeffective outer diameter measurement increases and does not flare ateach location in which the effective outer diameter measurement remainsconstant. In some embodiments, the support structure 40 flaresinitially, for example, at segment R_(n+1) due to an incrementallygreater width D1 relative to width D of R_(n), and then levels off atthe outflow end 36, for example due to a constant effective outerdiameter measurement due of the support structure at segments R_(n+1)and R_(n+2) (i.e. FIGS. 3B-3C). Those skilled in the art will readilyappreciate that the length of the initial flare or leveled off sectionof the outflow region 42 can vary as desired by increasing the widthsD1, or D2 and D3, respectively. In certain embodiments illustrated inFIGS. 3A through 3O (described above), any particular segment R(R_(n+1), R_(n+2), R_(n+3)) having width D (D1, D2, D3) can be providedwith an effective outer diameter measurement that increases at a greaterrate relative to a previous segment R. In certain embodimentsillustrated in FIGS. 3A through 3O (described above), any particularsegment R (R_(n+1), R_(n+2), R_(n+3)) having width D (D1, D2, D3) can beprovided with an effective outer diameter measurement that increases ata lesser rate relative to a previous segment R. It should be appreciatedby those of skill in the art that the flared outflow region 42 can beconfigured to alter the size and or shape of its flared appearance, aslong as the effective outer diameter measurement of the supportstructure 40 prior to combination with the biocompatible layer 50 toform the wall 30 increases along at least a portion of the outflowregion 42. Those skilled in the art will appreciate that the appearance(e.g., size, shape, or angle) of the flare in the outflow region 42depends, in part, on the widths D1, D2, D3 of each ring segment R_(n+1),R_(n+2), R_(n+3), respectively.

Various dimensions D (e.g., D, D1, D2, D3) for ring segments R (e.g.,R₁, R_(n), R_(n+1), R_(n+2), R_(n+3)) are contemplated for the supportstructure 40. Table 1 below provides non-limiting examples of dimensionsfor manufacturing a support structure 40 having an incrementallyincreasing effective outer diameter measurement D_(inc) in the outflowregion 42.

TABLE 1 Dimensions for Exemplary Ring Segments R_(n+1), R_(n+2), R_(n+3)Constant Effective Maximum Effective Outer Diameter Outer OutflowMeasurement D (R₁ −R_(n)) D1 (R_(n+1)) D2 (R_(n+2)) D3 (R_(n+3))Diameter(Uncovered) 6.0 mm 2.18 mm +− 2.51 mm +− 2.88 mm +− 3.10 mm +−11.4- 0.45 mm 0.45 mm 0.45 mm 0.45 mm 11.6 mm 7.0 mm 2.04 mm +− 2.35 mm+− 2.70 mm +− 2.90 mm +− 12.4- 0.45 mm 0.45 mm 0.45 mm 0.45 mm 12.6 mm8.0 mm 1.89 mm +− 2.17 mm +− 2.50 mm +− 2.69 mm +− 13.4- 0.45 mm 0.45 mm0.45 mm 0.45 mm 13.6 mm

In the exemplary embodiment shown in FIGS. 8A-8G outlet region 42 hasthe same flarable configuration, as shown in FIGS. 1A-2C and asdiscussed generally above. The inlet region 44 of this alternative stentgraft 10 may have a pre-fabricated and pre-extended flared configurationprior to implant, as shown in FIGS. 8A-8G. Various views of this stentgraft embodiment in which support structure 40 has a pre-fabricated andpre-extended outwardly flaring inflow region 44 for maintaining orimproving patency of the graft along inflow region 44. In theseexamples, the flared shape or appearance is oriented in the oppositedirection from the flared shape or appearance at outflow end 36. Thispre-fabricated and pre-extended flared configuration of inflow region 44facilitates friction fitted attachment and positioning within avasculature.

FIG. 8A shows a side view of the straight vascular graft shown in FIG.1A, illustrating the flared configuration of the inflow region 44 of thesupport structure 40 prior to combination with the biocompatible layer50 to form wall 30. FIG. 8B shows a schematic view of the straightvascular graft shown in FIG. 1A, illustrating the pre-fabricated,pre-extended flared configuration of the support structure 40 along theinflow region 44 and expandable out flow region 42 after combining thesupport structure 40 shown in FIG. 8A with the biocompatible layer 50 toform the wall 30. FIG. 8B shows the vascular graft after inflow region44 has been expanded. FIG. 8C shows a schematic view of the straightvascular graft shown in FIG. 1A, illustrating the expanded effectiveouter diameter measurement D_(exp) of the support structure 40 along theoutflow region 42. FIG. 8D shows a side wireframe view of the supportstructure 40 shown in FIGS. 8A and 8D. FIG. 8E is a photograph showingan actual construction of the support structure 40 shown in FIG. 8A.

With particular reference to FIG. 8E, it is evident that thepre-fabricated, pre-expanded flared shape or appearance of the inflowregion 44 is achieved by a similar design methodology to the onedescribed in FIG. 4 in which ring segments R₁ and R₂ of the supportstructure 40 are provided with different widths D2, D1, respectively,from each other, as well as different widths D from the ring segments R₃to R_(n), where n=an integer. The different widths D (e.g., D2, D1, D)of ring segments R (e.g., R₁, R₂, R₃ to R_(n), where n=an integer)impart the effective outer diameter measurements D_(inc) which providethe support structure 40 along the outflow region 42 with a flaredappearance.

The outflow region 42 of support structure 40 may be configured in thesame manner as that discussed above and shown in FIG. 4B. FIG. 8F showsa schematic view of the support structure 40 useful for inflow region 44according to an exemplary construction. The construction can be utilizedfor at least two objectives. In a first embodiment, the flared inflowregion 44 creates a pre-fabricated, pre-expanded flared configurationprior to implant. In another embodiment, the pre-expanded and flaredconfiguration provides a locally increased inside diameter that providesspace for receiving (e.g., as in a socket) a lumen distinct frombiocompatible layer 50, although possibly constructed of the same basematerial as biocompatible layer 50. For example, an extension lumen 51having a wall thickness that is thicker than layer 50 may be insertedinto the constructed socket such that the inner luminal surface of theextension lumen 51 will be substantially flush with or at least the sameapproximate diameter as the inner luminal surface of conduit bodyportion 43.

FIG. 8F shows a scaled illustration of the support structure 40 showingthe precise relative proportions of the support structure patterndepicted therein. Each ring forming conduit body portion 43 comprises aseries of peaks and valleys, best shown as R_(n) and R₃ in FIG. 8F. Thepeaks or crowns of each of these rings directly face and are alignedwith a corresponding valley of an adjoining ring, and struts connectingadjoining rings builds flexibility into the graft to facilitate in-situbending. A proximal inflow region 35 of support structure 40 includes aplurality of rings in which the peaks or crowns of a ring R₂ faces thepeaks and crowns of adjoining rings R₁ while the valleys of ring R2directly faces and aligns with valleys of adjoining rings R₁ to provideadditional stiffness at inflow region 35.

As is shown in FIG. 8F, ring segments R₁ and R₂, which are locatedproximal to the inflow end 35 of the inflow region 44 of the supportstructure 40, are provided with greater widths D₂, D₁, respectively,than ring segments R₃ to R_(n) (where n=an integer), which are locatedin the body region 43 of support structure 40. Providing ring segment R₂with a greater width D₁ than the width D of ring segment R₃ causes thewall 30 adjacent to ring segment R₂ to flare outward as illustrated bythe angled R₂ segment shown in FIG. 8D. The effective outer diametermeasurement D_(inc) of the inflow region 44 shown in this exampleconsists of ring segment R₁ which comprises a constant effective outerdiameter measurement along its width D₂, as is illustrated by the lineextending along the longitudinal width of ring segment R1 shown in FIG.8D. It should be appreciated by those skilled in the art, however, thatthe support structure 40 proximal to the inflow region 44 can beconfigured in any desirable manner which maximizes patency of the inflowregion while vascular graft 10 is implanted in a body lumen.

Looking now at FIGS. 2B and 8B, there is shown a schematic view of anembodiment of the vascular graft 10 shown in FIGS. 1A and 8A depictingthe generally uniform effective outer diameter measurement of thesupport structure 40 after combining the support structure 40 shown inFIGS. 2A and 8A with the biocompatible layer 50 to form the wall 30.Application of biocompatible layer 50 to an exterior surface of supportstructure 40 so as to form wall 30 places the support structure 40 inthe outflow region 42 under continuous compressive radial stress S(e.g., radial compressive stress) resulting from a continuous appliedload to support structure 40 by compressing the biocompatible layer 50against the support structure 40. Generally, the compressive stress Sresulting from the continuous applied load in the outflow region 42 isgreater than a compressive stress S₀ resulting from the applied load inthe body region 43. Those skilled in the art will appreciate that thecompressive stress S resulting from the continuous radially applied loadin the outflow region 42 generally changes along the length of outflowregion 42 as the effective outer diameter of the support structure 40 inthe outflow region 42 changes. As is shown in FIGS. 2B and 8B, forexample, the compressive stress S experienced by the support structure40 resulting from the continuous applied load in the outflow region 42incrementally increases along the length of support structure 40 as itapproaches outflow aperture 34, i.e. compressive stress S is greater ateach segment along the support structure 40 that is incrementally moredistal from the at least one inflow aperture 32 at the inflow end 35. Inthis example, the compressive stress S is at a minimum S_(min) at aproximal area of outflow region 42 and increases, as the effective outerdiameter of the support structure 40 (prior to combination with thebiocompatible layer 50 to form wall 30) increases, to a maximumcompressive stress S_(max) proximal to the outflow end 36.

The compressive stress S causes an elastic deformation of the supportstructure 40 in the outflow region 42. As will be appreciated by thoseskilled in the art, the extent of the elastic deformation is a functionof the compressive stress S resulting from the applied load caused bythe biocompatible layer 50. In the example shown in FIGS. 2B and 8B, theelastic deformation of the support structure 40 in the outflow region 42is incrementally greater at each segment along the support structure 40that is incrementally more distal from the at least one inflow aperture32, as illustrated by the increasing compressive stress from a minimumcompressive stress S_(min) to a maximum compressive stress S_(max).

In contrast to the deformation inducing compressive stress S along theoutflow region 42, a compressive stress S₀ resulting from an appliedload by biocompatible layer 50 at inflow distal end 35 and body region43 causes only negligible elastic deformation of the support structure40 along the body region 43. For the sake of clarity, it is to beunderstood by those skilled in the art that the negligible compressivestress S₀ experienced by the support structure 40 in the body region 43resulting from the applied load caused by the biocompatible layer 50against the support structure 40 is negligible relative to the amount ofcompressive stress S (S_(min) to S_(max)) experienced by the supportstructure 40 in the outflow region 42 resulting from the applied loadcaused by the biocompatible layer 50 against the support structure 40.As used herein, negligible compressive stress S₀ refers to an amount ofcompressive stress that is not accompanied by or associated with achange in the effective outer diameter, or is accompanied by orassociated with only a very minor amount of change in the effectiveouter diameter, of the portion or region of the support structure 40experiencing the compressive stress S, as will be appreciated by thoseskilled in the art. In contrast to the negligible compressive stress S₀experienced by the support structure 40 in the body region 43 aftercombination with the biocompatible layer 50 to form wall 30, the supportstructure 40 in the outflow region 42 after combination with thebiocompatible layer 50 to form wall 30 experiences a substantial amountof compressive stress that generally changes as the effective outerdiameter measurement of the support structure 40 prior to combinationwith biocompatible layer 50 to form wall 30 changes. As used herein,“substantial compressive stress” and “continuous compressive stress” areused interchangeably herein to mean an amount of compressive stress thatis accompanied by or associated with a change in the effective outerdiameter of the portion or region of the support structure 40experiencing the compressive stress S in the radial direction, as willbe appreciated by those skilled in the art.

The combination of the incrementally greater elastic deformation of thesupport structure 40 along the outflow region 42 with the absence ofelastic deformation of the support structure 40 along the body region 43imparts the conduit 20 with a uniform effective outer diametermeasurement, as is illustrated in FIGS. 2B and 8B. This effective outerdiameter measurement comprises a constant effective outer diametermeasurement D_(c) along the body region 43 and a constrained effectiveouter diameter measurement D_(con) along the outflow region 42. As usedherein, “constrained” in connection with “effective outer diametermeasurement” refers to the effective outer diameter measurement of thesupport structure 40 along the outflow region 42 under the compressivestress S relative to the effective outer diameter measurement of thesupport structure 40 along the outflow region 42 in the absence ofcompressive stress S prior to combination of the support structure 40with the biocompatible layer 50 to form the wall 30. The constrainedeffective outer diameter measurement D_(con) is approximately equal tothe constant effective outer diameter measurement D_(c). Notably, thecompressive stress S resulting from the continuous applied loadmaintains the support structure 40 along the outflow region 42 at theconstrained effective outer diameter measurement D_(con).

The elastic deformation of the support structure 40 along the outflowregion 42 is reversible. The extent to which the elastic deformation ofthe support structure 40 along the outflow region 42 can be reverseddepends on a variety of factors, including the length D (e.g., D1, D2,D3) of each ring segment R (e.g., R_(n+1), R_(n+2), R_(n+3)), and theamount of counter force applied to the support structure 40 in theoutflow region 42, as will be appreciated by those skilled in the art.In this regard, a counter force comprising a radial expansion forceapplied to the support structure 40 in the outflow region 42 causesplastic deformation of the biocompatible layer 50. Such counter forcecauses a reduction of the compressive stress S experienced by thesupport structure 40. In other words, as the counter force increases theplastic deformation of the biocompatible layer 50, the compressivestress S experienced by the support structure 40 decreases, reversingthe plastic deformation of the support structure 40.

Focusing now on FIGS. 2C and 8C, there is shown a schematic view of anembodiment of the vascular graft 10 shown in FIGS. 1A and 8A depictingthe expanded effective outer diameter measurement D_(exp) of the supportstructure 40 of the vascular graft shown in FIGS. 2B and 8B, afterexpanding the outflow region 42 of the support structure 40. As notedabove, the expanded effective outer diameter measurement D_(exp) of thesupport structure 40 along the outflow region 42 results uponapplication of a counter force comprising a radial expansion force. Thepresent invention contemplates the use of any suitable means forapplying such radial expansion force, for example, by advancing aradially expandable device (e.g., a balloon catheter 98) along theinternal lumen of the conduit 20 from the at least one inflow aperture32 toward the outflow aperture 34 and expanding the radially expandableelement. Other suitable means for applying such radial expansion forceare apparent to the skilled artisan.

Those skilled in the art will further appreciate that the presentinvention contemplates the use of any amount of counter force comprisinga radial expansion force which is capable of overcoming the continuousapplied load contributed by the biocompatible layer 50 and thus permitsexpanding the outflow region 42. Preferably, the amount of counter forcecomprising the radial expansion force used is an amount that results inthe atraumatic expansion of the outflow region 42 within a body lumen.Exemplary ranges of such counter forces will be apparent to the skilledpractitioner. For the sake of clarity, however, an exemplary range ofcounter forces which can result in the atraumatic expansion of theoutflow region 42 in vivo or in situ includes those counter forces whicharise from using a semi-compliant balloon that is no more than 2.5 mm(more preferably no more than 2.0 mm) over the effective outer diametermeasurement of the outflow region 42.

Following application of a counter force comprising a radial expansionforce applied to the support structure 40 in the outflow region 42, thegraft reconfigures in such a way as to result in a plastically deformedbiocompatible layer 50. In some instances, following application of acounter force, the vascular graft 10 reconfigures in such a way as toresult in a plastically deformed biocompatible layer 50 and acompressive stress S experienced by the support structure 40 that isless than the compressive stress S experienced by the support structureprior 40 to application of the counter force. In some instances,following application of a counter force, the graft reconfigures in sucha way as to result in the support structure 40 experiencing residualcompressive stress S where there was previously continuous compressivestress S (e.g., substantial compressive stress) experienced by thesupport structure 40 prior to application of the counter force. As usedherein, “residual compressive stress” means an amount of compressivestress S that remains partially as a result of recoil associated withplastic deformation of the biocompatible layer 50 upon application ofthe counter force comprising the radial expansion force. Those skilledin the art will appreciate that the amount of such residual compressivestress depends on a variety of factors, including the magnitude of theradial expansion force and the amount of compressive stress Sexperienced by the support structure 40 due to the continuous appliedload caused by the biocompatible layer 50 against the support structure40 before application of the counter force, for example.

Still looking at FIGS. 2C and 8C, it is evident that a counter forcecomprising a radial expansion force applied to the support structure 40in the outflow region 42 reconfigures the support structure 40 in to theoutflow region 42 from the constrained effective outer diametermeasurement D_(con) shown in FIGS. 2B and 8B to an expanded effectiveouter diameter measurement D_(exp) shown in FIGS. 2C and 8C that isgreater than the constrained effective outer diameter measurementD_(con) along at least a portion of the support structure 40 in theoutflow region 42. In one embodiment, the change in diameter between theconstrained effective outer diameter measurement D_(con) and theexpanded effective outer diameter measurement D_(exp) is about 0.5 mm toabout 2.5 mm or about 1 mm to about 2 mm, and even more 1 mm to 1.5 mm.In accordance with another example embodiment, the expanded effectiveouter diameter measurement D_(exp) is at least 1 mm greater than theconstrained effective outer diameter measurement D_(con) along at leasta portion of the support structure 40 in the outflow region 42. Ofcourse, the expanded effective outer diameter measurement D_(exp) can beat least 1.10 mm, at least 1.20 mm, at least 1.30 mm, at least 1.40 mm,at least 1.50 mm, at least 1.60 mm, at least 1.70 mm, at least 1.80 mm,at least 1.90 mm, at least 2.0 mm, at least 2.10 mm, at least 2.20 mm,at least 2.30 mm, at least 2.40 mm, at least 2.50 mm, at least 2.60 mm,at least 2.70 mm, at least 2.80 mm, at least 2.90 mm, at least 3.0 mm,at least 3.10 mm, at least 3.20 mm, at least 3.30 mm, at least 3.40 mm,at least 3.50 mm, at least 3.60 mm, at least 3.70 mm, at least 3.80 mm,at least 3.90 mm, at least 4.0 mm, at least 4.10 mm, at least 4.20 mm,at least 4.30 mm, at least 4.40 mm, at least 4.50 mm, at least 4.60 mm,at least 4.70 mm, at least 4.80 mm, at least 4.90 mm, or 5.0 mm or moregreater than the constrained effective outer diameter measurementD_(con) along at least a portion of the support structure 40 in theoutflow region 42, depending on various factors, such as magnitude andduration of the radial expansion force and the length D (e.g., D1, D2,D3, etc.) or amount of ring segments R (e.g., R_(n+1), R_(n+2), R_(n+3),etc.) as will be appreciated by those skilled in the art. In accordancewith another example embodiment, the expanded effective outer diametermeasurement D_(exp) of the support structure 40 along the outflow region42 after being reconfigured is at least 1.0 mm greater than theconstrained effective outer diameter measurement D_(con) along theentire portion of the support structure 40 in to the outflow region 42.In certain example embodiments, the expanded effective outer diametermeasurement D_(exp) can be at least 1.10 mm, at least 1.20 mm, at least1.30 mm, at least 1.40 mm, at least 1.50 mm, at least 1.60 mm, at least1.70 mm, at least 1.80 mm, at least 1.90 mm, at least 2.0 mm, at least2.10 mm, at least 2.20 mm, at least 2.30 mm, at least 2.40 mm, at least2.50 mm, at least 2.60 mm, at least 2.70 mm, at least 2.80 mm, at least2.90 mm, at least 3.0 mm, at least 3.10 mm, at least 3.20 mm, at least3.30 mm, at least 3.40 mm, at least 3.50 mm, at least 3.60 mm, at least3.70 mm, at least 3.80 mm, at least 3.90 mm, at least 4.0 mm, at least4.10 mm, at least 4.20 mm, at least 4.30 mm, at least 4.40 mm, at least4.50 mm, at least 4.60 mm, at least 4.70 mm, at least 4.80 mm, at least4.90 mm, or 5.0 mm or more greater than the constrained effective outerdiameter measurement D_(con) along the entire portion of the supportstructure 40 in the outflow region 42, as will be appreciated by thoseskilled in the art.

The support structure 40 can be constructed from any material thatenables the support structure 40 in the outflow region 42 to reconfigurefrom a constrained effective outer diameter measurement D_(con) to anexpanded effective outer diameter measurement D_(exp) upon applicationof the counter force. In accordance with one example embodiment, thesupport structure 40 is constructed from a shape memory alloy. Exemplaryshape memory alloys can be formed from a combination of metalsincluding, but not limited to: aluminum, cobalt, chromium, copper, gold,iron, nickel, platinum, tantalum, and titanium. In accordance with oneexample embodiment, the support structure 40 is constructed fromnitinol. Other shape memory alloys or other materials which can be usedto construct the support structure 40 are apparent to the skilledartisan.

Those skilled in the art will appreciate that the support structure 40can be constructed with a larger or smaller expandable portion. Theskilled artisan will also appreciate that the same methodology describedabove in connection with FIG. 3 which enables outflow region 42 to beexpandable can be applied to render other portions of the supportstructure 40 expandable (e.g., the body region).

The biocompatible layer 50 can be constructed from any biocompatiblematerial. The material may further be substantially impermeable to fluidin certain embodiments. The material is capable of causing a continuousapplied load to place the support structure 40 under a sufficientcontinuous compressive stress (e.g., substantial compressive stress asdefined herein) to maintain the constrained effective outer diametermeasurement D_(con) of the support structure 40 along the outflow region42 after combining the support structure 40 with the biocompatible layer50 to form the wall 30. In accordance with an example embodiment, thebiocompatible layer 50 comprises an expandable polymer. In accordancewith an example embodiment, the biocompatible layer 50 comprisesexpanded polytetrafluoroethylene (ePTFE).

Generally, as is shown in FIGS. 2B-2C and 8B-8C, the biocompatible layer50 extends at least along the entire longitudinal length of the supportstructure 40 from the inflow end 35 to the outflow end 36. As will beappreciated by those skilled in the art, the biocompatible layer 50 mayextend at least partially beyond, or fall short of, the inflow end 35and the outflow end 36 in accordance with acceptable manufacturingspecifications. In accordance with one example embodiment, thebiocompatible layer 50 can extend beyond the edge of the inflow end 35and the outflow end 36 and wrap around at least a portion of theinterior surface of the support structure 40 in the form of a cuff.

Referring to FIGS. 5A, 5B, 5C and 5D, there are shown examplecross-sections of vascular graft 10 shown in FIGS. 1A and 8A, depictingvarious ways in which the biocompatible layer 50 can be configured. Ascan be seen in the exemplary embodiments of FIGS. 5A and 5C, thebiocompatible layer 50 can comprise a biocompatible outer layer 54 and aseparate biocompatible inner layer 55 spaced apart therefrom such thatouter layer 54 and inner layer 55 are positioned on opposite sides ofsupport structure 40. As shown in FIGS. 5A and 5B, the biocompatibleouter layer 54 and the biocompatible inner layer 55 can be configured asdistinct layers of the same substrate continuously wrapped around an endof the support structure 40 or instead as two separate substrates (i.e.,non-continuous) that are positioned at opposite sides of the supportstructure 40. In this example, either the biocompatible outer layer 54or the biocompatible inner layer 55 may extend at least partially beyondand wrap around the edge of the inflow end 35 and outflow end 36 to forma cuff, for example, to minimize damage to surrounding tissue duringdeployment of the vascular graft 10. The circled portion of FIG. 5A isrepresented as FIG. 5B and shows an exploded view of a portion of thebiocompatible layer 50 showing how the biocompatible outer layer 54 andthe biocompatible inner layer 55 conform to each other and the supportstructure 40 as a result of how the layers may be applied, heated,sintered, or otherwise adhered on or to the support structure 40,methods of which are known to those of skill in the art. As shown in theexample embodiment in FIG. 5B, the biocompatible layer 50 can comprise abiocompatible outer layer 54 without a biocompatible inner layer 55.Those skilled in the art will appreciate, however, that thebiocompatible inner layer can help to decrease the likelihood ofstenosis or occlusion in the conduit 20 of the vascular graft 10 or toalter the fluid impermeability of the wall 30. FIGS. 5A-5D show anexample embodiment of the vascular graft 10 in which the biocompatiblelayer 50 encapsulates the support structure 40 with the biocompatibleouter layer 54 and the biocompatible inner layer 55. In this example,the biocompatible outer layer 54 and the biocompatible inner layer 55can be configured to encapsulate the support structure 40. All knownmethods and structures relating to the application or use of abiocompatible layer such as those described herein are anticipated foruse in conjunction with the present invention, such that the form of thelayer on the support structure is not limited by the particularillustrative examples provided herein.

In an exemplary embodiment, biocompatible layer 50 is configured as asheath, sleeve or other covering that binds and applies a compressivestress to support structure 40. In an exemplary embodiment,biocompatible layer 50, particularly biocompatible outer layer 54, isadhesively bound to an exterior surface of support structure 40 forminga constricting and continuous covering over support structure 40. Thecovering may be constructed from any suitable biocompatible material,particularly ePTFE that is processed to apply a compressive forceagainst support structure 40. In an exemplary embodiment, biocompatiblelayer 50, including biocompatible outer layer 54 and/or biocompatibleinner 55 form hemocompatible coverings configured and adapted forengaging tissue and/or blood. It should be appreciated that thebiocompatible layer 50 described herein is distinguishable from a meresurface modifying coating that is conventionally applied to medicaldevices for purposes of delivering a therapeutic agent or changing thesurface characteristics of a medical device, for example, a hydrophiliccoating. Nevertheless, it is contemplated that such surface-modifyingcoatings, for example a coating comprising a biological oil or fat, asis described in U.S. Pat. No. 8,124,127 (which is incorporated herein byreference in its entirety), can be used to coat at least a portion of asurface of the support structure 40 or the biocompatible outer 54 andinner 55 layers, for reasons that would be evident to those skilled inthe art. For example, it may be desirable to coat at least a portion ofthe interior surface of support structure 40 or the biocompatible innerlayer 55 with a cured fish oil coating containing an anti-clottingtherapeutic agent to prevent or minimize occlusion of the implantedgraft.

Turning now to FIG. 1B, an alternative embodiment of a vascular graft10′ is shown. Whereas the example shown in FIG. 1A depicts a straightvascular graft 10, the vascular graft 10′ of FIG. 1B may be designed toinclude a second inflow aperture 33 to provide a bifurcated or generallyT-shaped vascular graft 10′, as is depicted in the example shown in FIG.1B. It is to be understood that any description given with respect tocomponents common to both of the grafts 10 and 10′ (i.e., thosecomponents identified with the same reference numerals) is generallyapplicable to both of the embodiments, unless otherwise indicated. As isshown in FIG. 1B, a longitudinal axis of the second inflow aperture 33intersects a longitudinal axis of the at least one inflow aperture 32 ata non-parallel angle. As used herein, “non-parallel angle” means anangle in which the longitudinal axis of the at least one inflow aperture32 is not parallel to the longitudinal axis of the second inflowaperture 33 (e.g., greater than 0°). The non-parallel angle can be anynon-parallel greater than 0° and less than 180° depending on theparticular arrangement needed for the graft implantation. Preferably,the non-parallel angle at which the longitudinal axis of the secondinflow aperture 33 intersects the longitudinal axis of the at least oneinflow aperture 32 is between about 25° and about 45°. In accordancewith one example embodiment, the non-parallel angle at which thelongitudinal axis of the second inflow aperture 33 intersects thelongitudinal axis of the at least one inflow aperture 32 is about 35°.

FIGS. 6A, 6B, and 6C show various views of embodiments of a supportstructure 40 of the bifurcated vascular graft 110 construction shown inFIG. 1B, illustrating the support structure 40 prior to combination withthe biocompatible layer 50 to form the wall 30 (FIG. 6A), aftercombining the support structure 40 shown in FIG. 6A with thebiocompatible layer 50 to form wall 30 (FIG. 6B), and after expandingthe outflow region 42 of the biocompatible layer 50 covered supportstructure 40 of the vascular graft 110 shown in FIG. 6B (FIG. 6C). Thoseskilled in the art will appreciate that the description of thestructure, function, and components of the straight vascular graft 110above in connection with FIGS. 2A-5C is equally applicable to thebifurcated vascular graft 110 shown in FIGS. 6A-6C.

Referring now to FIGS. 7A-7C, there is shown in a top view (FIG. 7A), atop wireframe view (FIG. 7B), and a side wireframe view (FIG. 7C) of anembodiment of a support structure of the vascular graft shown in FIGS.1B, 6A-6C, depicting the support structure with only at least one inflowaperture 32 (see, e.g., FIG. 5A) and an outflow aperture 34 (see, e.g.,FIG. 5C) before the second inflow aperture 33 is attached to the graftbody to form the bifurcated vascular graft 10′ shown in FIGS. 1B and6A-6C. As will be appreciated by those skilled in the art, the supportstructure 40 featured in FIGS. 7A-7C includes all of the pertinentfeatures of the vascular graft 10′ shown in FIGS. 6A-6C. FIG. 7A shows aproperly scaled illustration of the support structure 40 showing theprecise relative proportions of the support structure and itsstrut/stent pattern. As shown in the example embodiment in FIGS. 7A-7B,the support structure also includes a junction aperture 37 to which ahollow branch conduit 99 is connected. Junction aperture 37 and thesecond inflow aperture 33 of branch conduit 99 is in fluid communicationwith the at least one inflow aperture 32 and outflow aperture 34. As isshown in the example in FIG. 7A, the support structure 40 can terminatein one or more blunt ends 41, for example, to prevent or minimize damageto the biocompatible layer 50 caused by the support structure 40. Theblunt ends 41 can be formed in a keyhole like shape as shown in FIG. 7A,or any other shape which enables the blunt ends 41 to prevent orminimize damage to the biocompatible layer 50 by the support structure40.

To facilitate attachment of the branch conduit 99 and its second inflowaperture 33 to the body region 43 of the support structure 40 atjunction aperture 37, a depression 39 is provided in the contour of thebody region 43 of support structure 40, as is illustrated in the exampleembodiment in FIG. 7C. Branch conduit may then be sewn, sintered orotherwise attached to body region 43 at depression 39.

Turning now to FIGS. 9A-9H, there is shown various views of anotherembodiment of the bifurcated vascular graft 410 similar to that shown inFIGS. 1B, 6A-6C and having a branch conduit 99 with a pre-fabricated andpre-expanded flared configuration at second inflow aperture 33 of thebranch conduit 99 prior to implantation. With the exception of thisflared configuration, the vascular graft 410 may have the samestructure, components and configuration as that of the vascular graft110 of FIGS. 1B and 6A-6C. This pre-fabricated, pre-expanded flaredconfiguration anchors and provides rigidity and structure to theadjoining conduit body 43. The flared end may also facilitate vascularattachment and implantation. FIG. 9A shows a side view of an embodimentof a support structure 40 of the bifurcated vascular graft 110 shown inFIGS. 1B, 6A-6C, illustrating the support structure 40 prior tocombination with the biocompatible layer 50 to form wall 30. FIG. 9Bshows a schematic view of an embodiment of the bifurcated vascular graft110 shown in FIG. 1B, 6A-6C after combining the support structure 40shown in FIG. 9A with the biocompatible layer 50 to form wall 30. FIG.9C shows a schematic view of an embodiment of the bifurcated vasculargraft 410 construction shown in FIGS. 1B and 6A-6C after expanding theoutflow end 36 of the support structure 40 of the bifurcated vasculargraft 410 shown in FIG. 9B. FIG. 9D is a photograph showing a workingprototype of the embodiment of the support structure 40 shown in FIG.9A. FIG. 9E is a photograph of a working prototype of the embodiment ofthe bifurcated vascular graft shown in FIG. 9B, depicting theconstrained effective outer diameter measurement D_(con) of the supportstructure 40 along the outflow region 42. FIG. 9F is a photograph of aworking prototype of the embodiment of the bifurcated vascular graftshown in FIG. 9C, depicting the expanded effective outer diametermeasurement D_(exp) of the support structure 40 along the outflow region42 and an expanded effective outer diameter measurement D_(exp) along aninflow region 44 proximal to the second inflow aperture 33. FIG. 9G isanother photograph similar to FIG. 9F further illustrating a border 94which is used in FIG. 9H to show schematically as a detail view of arepresentative cross-section of an embodiment of FIGS. 9B and 9C.

Referring to FIG. 9G, an extension conduit 51 is shown assembled to aflared socket-like construction. Utilizing the flared second inflowaperture 33, the extension conduit can connect to the luminal surface ofbranch conduit 99 when the branch conduit is covered with thebiocompatible layer on one or both of the interior and exterior surfacesof the branch's support structure. When an extension conduit comprisinga thicker wall 89 than the wall thicknesses 87 and 88 of the innerbiocompatible layer 55 and outer compatible layer 54 respectively, theenlargened inner diameter of the branch provides sufficient room for theextension conduit to have a diameter that is substantially the same asthe inner diameter of all or at least a majority of the branch conduit'sinner luminal diameter.

Those skilled in the art will appreciate that in the example embodimentsshown in FIGS. 9A-9G, the bifurcated vascular graft 110 and variousfeatures of the support structure 40 function in substantially the sameway as described in the relevant paragraphs above.

In accordance with one example embodiment, a vascular graft 110comprises: a conduit 20 having a wall 30, the conduit 20 comprising: atleast one inflow aperture 32 at an inflow end 35 at a body region 43;and an outflow aperture 34 at an outflow end 36 at an outflow region 42opposite from the at least one inflow aperture 32; wherein the wall 30comprises a support structure 40 and a biocompatible layer 50; whereinprior to combination with the biocompatible layer 50 to form the wall30, the support structure 40 comprises multiple effective outer diametermeasurements along its length comprising a constant effective outerdiameter measurement D_(c) along the body region, and an effective outerdiameter measurement D_(inc) along the outflow region that isincrementally greater at each segment along the support structure 40that is incrementally more distal from the at least one inflow aperture32; wherein after combination with the biocompatible layer 50 to formthe wall 30, the support structure 40 in the outflow region 42 is undercontinuous compressive stress S resulting from a continuous applied loadcaused by the biocompatible layer which maintains the support structure40 in the outflow region at a constrained effective outer diametermeasurement D_(con) that is not incrementally greater at each segmentalong the support structure that is incrementally more distal from theat least one inflow aperture; and wherein after application of a counterforce to the support structure 40 in the outflow region 42 the outflowregion 42 is reconfigured from the constrained effective outer diametermeasurement D_(con) to an expanded effective outer diameter measurementD_(exp), at least a portion of which is at least one millimeter greaterthan the constrained effective outer diameter measurement D_(con).

The straight and bifurcated or T-shaped vascular grafts (e.g., thegrafts 10 and 110) of the present invention can be used for a variety ofapplications, including, for example, for replacement or bypass ofdiseased vessels in patients suffering from occlusive or aneurysmaldiseases, in trauma patients requiring vascular replacement, fordialysis access, to improve flow dynamics and reduce arterializedpressure during surgical anastomosis, or other vascular proceduresroutinely performed by a medical practitioner, as will be apparent tothose skilled in the art.

In operation, the present taught vascular grafts (e.g., the grafts 10and 110) are deployed for implantation into a body passage (e.g., ablood vessel). Embodiments of the present invention contemplate anyoperable method of deploying a vascular graft 10/110 for implantationinto a body passage safely and effectively. Suitable methods will beapparent to the skilled medical practitioner. For example, one knownmethod of deploying such a graft is to use a sheath with a tear line or“rip cord”. The graft is contained within one or more sheaths fordelivery to the desired location, preferably in a compressed conditionsuch that the outer diameter of the sheath(s) is 2 or more millimeterssmaller than the vessel the graft (or graft portion) is intended to beimplanted within. Once properly located, a cord is pulled to separatethe sheath along a tear line, and the sheath is then unwrapped from thegraft and removed, leaving the graft in place at least partially due tothe graft's self-expanding qualities. The general method of installing agraft using a single sheath in this manner is well known in the art, andas such requires no further description.

Once implanted in a body passage, the outflow region 42 of the vasculargraft 10 can be expanded to maintain or restore patency of the graft,even after extensive duration of time passing from the time of originalimplantation (e.g., weeks, months, years). For example, if a portion ofthe graft collapses (e.g., due to tissue in-growth and eventuallythrombosis formation), becomes stenosed, or sustains intimalhyperplasia, patency can be restored by expanding the outflow region 42of the vascular graft 10 according to inventive methods describedherein.

FIGS. 10A and 10B are schematic illustrations of an expandable devicebeing used to expand the outflow region 42 of an embodiment of vasculargraft 10 which is provided with a bifurcated construction, although mayalso be employed for non-bifurcated constructions. More specifically,FIG. 10B is a detail view taken about the border 86 of FIG. 10A. In theexample shown in FIGS. 10A-10B, the expandable device comprises aballoon catheter 98 with a balloon 97. Those skilled in the art,however, will appreciate that any expandable device which is capable ofapplying a counter force comprising a radial expansion force can beused. FIGS. 10A-10B are also instructive as to the installation of thegraft 110 illustrated in this embodiment.

FIG. 11 is a photograph demonstrating an expandable device 86 being usedto expand an outflow region 42 of a vascular graft 110 which is providedwith a bifurcated construction. The expandable device would be equallyapplicable to straight vascular grafts such as vascular graft 10.

Those skilled in the art will readily envision a variety of methods forexpanding an outflow region 42 of the vascular graft 10.

In accordance with an example embodiment, a method 100 of expanding anoutflow region 42 of an implanted vascular graft 10 generally comprisesthe steps of (a) identifying or providing 102 a vascular graft 10 havinga support structure configured with a flared outflow region 42 accordingto any aspect of the present invention; and (b) applying a counter force108 to the support structure 40 in the flared outflow region 42 toexpand the outflow region 42.

In step 102, the implanted vascular graft 10 comprises: a conduit 20having a wall 30, the conduit 20 comprising: at least one inflowaperture 32 at an inflow end 35 of a body region 43; and an outflowaperture at the outflow end of an outflow region 42 opposite from the atleast one inflow aperture 32; wherein the wall comprises a supportstructure 40 and a biocompatible layer 50; wherein the support structure40 in the outflow region 42 is under compressive stress S resulting froman applied load caused by the biocompatible layer 50. In step 108,applying a counter force to the support structure 40 in the outflowregion 42 reconfigures the support structure 40 in the outflow region 42from a constrained effective outer diameter measurement D_(con) to anexpanded effective outer diameter measurement D_(exp) that is greaterthan the constrained effective outer diameter measurement D_(con),thereby expanding the outflow region 42 of the implanted vascular graft10.

FIG. 12 shows a flow chart depicting an exemplary embodiment of a method100 of expanding an outflow region 42 of a vascular graft 10 accordingto one aspect of the present invention.

As shown in the exemplary embodiment in FIG. 12, a method of expandingan outflow region 42 of an implanted vascular graft 10 includes steps102 to 108. Step 102 comprises: (a) identifying an implanted vasculargraft 10 described herein. To expand the implanted vascular graft 10identified in step 102, step 108 is conducted. Step 108 comprises: (b)applying a counter force to the support structure 40 in the outflowregion 42 in accordance with the detailed description herein, therebyexpanding the outflow region 42 of the implanted vascular graft 10.

It should be appreciated that although the expandable outflow region 42can be expanded at any time post-implantation, in practice the outflowregion is advantageously expanded when the outflow region 42 hascollapsed or stenosed or has sustained intimal hyperplasia. In suchinstances, the outflow region 42 that has collapsed, stenosed, orsustained intimal hyperplasia impairs patency of a vessel in which theimplanted vascular graft 10 is implanted.

In an exemplary embodiment, applying the counter force comprisesexpanding an expandable device in the outflow region 42 of the implantedvascular graft 10. In an exemplary embodiment, prior to expanding theexpandable device (step 108) the expandable device is advanced to theoutflow end (step 106).

In an exemplary embodiment, prior to advancing the expandable device tothe outflow region (step 106), the expandable device is introduced intothe implanted graft percutaneously (step 104). In an exemplaryembodiment, after expanding the expandable device 10, the expandabledevice is removed according to step 110.

In an exemplary embodiment, the expanded effective outer diametermeasurement D_(exp) is at least one millimeter greater than theconstrained effective outer diameter measurement D_(con). In anotherexemplary embodiment, the expanded effective outer diameter measurementD_(exp) is at least one millimeter greater than the constrainedeffective outer diameter measurement D_(con) along any portion of thesupport structure 40 in the outflow region 42.

Contemplated herein are various methods for making a vascular graft 10disclosed herein.

FIG. 13 is a flow chart depicting an exemplary method 200 of making avascular graft 10 according to one aspect of the present invention.

In an exemplary embodiment, a method 200 of making a vascular graft 10having an expandable outflow region comprises steps 202 to 209. In theexample shown in FIG. 13, the method 200 proceeds with: (a) providing asupport structure (step 202) in accordance with the detailed descriptionprovided herein. comprising at least one inflow aperture 32 at an inflowend 35 of a body region 43 and an outflow aperture 34 at an outflow end36 of an outflow region 42 opposite from the at least one inflowaperture 32. The support structure 40 may be sized through the use ofvarious mandrels to have multiple effective outer diameter measurementscomprising a constant effective outer diameter measurement D_(c) alongthe body region 43 of the support structure 40 in addition to anincrementally increasing effective outer diameter measurement D_(inc)along the outflow region 42 of the support structure. It should beappreciated by those skilled in the art that the support structure 40provided in step 202 can include any support structure 40 contemplatedherein, including the embodiments shown in FIGS. 2A, 5A, 7A, and 8A,which can be provided with an inflow region 44 or outflow region 42 witha flared configuration illustrated in FIGS. 3A-3O, or any combinationthereof.

Once the support structure 40 is provided in step 202, the method 200proceeds with step 204 which comprises: (b) combining the supportstructure 40 with at least one biocompatible layer 50 to form a conduit20 having a wall 30 comprising the support structure 40 and the at leastone biocompatible layer 50.

After combining the support structure 40 with the biocompatible layer 50in step 204, the method continues with step 206 which comprises: (c)inserting a mandrel into the outflow aperture 34 proximal to the outflowend 36 of the support structure 40.

With the mandrel inserted into the outflow aperture 34, the methodproceeds with step 208, which comprises: (d) constraining theincrementally increasing effective outer diameter measurement D_(inc)along the outflow region 42 of the support structure 40, for examplewith a compression wrap, in such a way that a continuous compressivestress S results from a continuous applied load caused by thebiocompatible layer 50 which maintains the support structure 40 alongthe outflow region 42 in a constrained effective outer diametermeasurement D_(con) that is generally uniform with the constanteffective outer diameter measurement D_(c).

To conform the biocompatible layer 50 to the support structure 40, themethod comprises step 209 of (e) sintering the biocompatible layer 50 ata segment in the outflow region 42.

FIG. 14A is a photograph illustrating step 206 of a method 200 of makinga vascular graft 10 according to one aspect of the present invention inwhich a mandrel is inserted into the outflow end 36 of the vasculargraft 10 prior to constraining the effective outer diameter measurementalong the outflow end of the support structure 40 with a compressionwrap.

FIG. 14B is a photograph illustrating a step 206 of a method 200 ofmaking a vascular graft 10 according to one aspect of the presentinvention in which a compression wrap is used to constrain the effectiveouter diameter measurement along the outflow end of the supportstructure 40.

In another exemplary embodiment of the invention, a vascular graft 510is illustrated in FIGS. 15A-C. The graft 510 is formed by a pair ofbifurcated graft subassemblies 302 a and 302 b (collectively, the“bifurcated subassemblies 302”), arranged as mirror images of eachother, and connected by an extension conduit 51. Each of the bifurcatedsubassemblies 302, may be arranged, as illustrated, to resemble thebifurcated vascular grafts 110. As discussed in more detail with respectto FIGS. 16A-16C and 17A-17C, further vascular graft embodiments can beformed by exchanging one or both of the bifurcated subassemblies 302with graft subassemblies resembling the graft 10. Accordingly, thecomponents of the graft 510 that are akin to those of the grafts 10and/or 110 (e.g., the conduit 20, the wall 30, the support structure 40,the biocompatible layer 50, etc.), have correspondingly been given thesame reference numerals as those used with respect to the abovediscussion of the grafts 10 and 110.

FIG. 15A illustrates the bifurcated subassemblies without abiocompatible layer 50, while FIG. 15B illustrates the bifurcatedsubassemblies with both the biocompatible layer 50 and an extensionlumen 51 establishing a continuous conduit between the subassemblies. Invarious embodiments, the extension lumen 51 may be a multilayer laminateconfiguration of ePTFB and has a thickness 89 greater than the thicknessof the inner layer 55 and outer layer 54 of biocompatible layer 50.

As illustrated in FIG. 15C, the bifurcated subassemblies 302 a and 302 bare insertable within a first vessel portion 306 a and a second vesselportion 306 b, respectively (collectively the vessel portions 306). Theconduit section 51 is arranged as a luminal structure that providesfluid communication, e.g., blood flow, between the bifurcatedsubassemblies 302, and therefore, the vessel portions 306. Due to thebifurcations of both of the subassemblies 302, at least a portion ofblood flow, i.e., the blood flow that is not diverted into the conduitsection 51, may also continue through and past the subassemblies 302.The wall 30 of the conduit section 51 may be unreinforced, that is,including only the biocompatible layer 50 and not the support structure40. It is to be appreciated that the conduit section 51 may be anydesired length. For example, relatively shorter lengths may be used insome embodiments, e.g., to bridge or bypass an occlusion in a bloodvessel, while relatively longer lengths are used in other embodiments,e.g., to connect an artery to a vein for assisting in dialysis. In oneembodiment, the conduit section 51 is between about 20 mm and 150 mm,although other lengths are also possible.

It is to be appreciated that the graft 510 may be used in embodiments inwhich the vessels 306 are different parts of the same vessel, or inembodiments in which the vessel portions 306 are parts of differentvessels. For example, if the vessel portions 306 are part of the samevessel, the graft 510 may be used to create a bypass of a section of thevessel located between the vessel portions 306 a and 306 b. For example,an occlusion, such as plaque buildup, may completely or partially impedeor block blood flow within a blood vessel of a patient. In this example,the graft 510 may accordingly be installed such that the conduit section51 provides a bypass of the occlusion when the subassemblies 302 areinstalled into the blood vessel on opposite sides of the occlusion.

As another example, in one embodiment, one of the vessel portions 306(e.g., the vessel 306 a) is a part of an artery, and the other of thevessel portions (e.g., the vessel 306 b) is part of a vein. In this way,the conduit section 51 diverts a portion of blood flowing through theartery into the vein. For example, this embodiment may be particularlyuseful in that the conduit section 51 may provide a suitable target toassist a patient in undergoing dialysis, e.g., with the blood divertedbetween the artery and vein taken from and re-injected into the conduitsection 51, thus avoiding unnecessary damage to a patient's vasculaturethat may result from repeated dialysis treatments. In such embodiments,the ability for the conduit section 51 to seal after needle punctures isenhanced versus the properties of the vascular graft 510 that might becovered by a thinner material than used in the conduit section 51.

A vascular graft 610 is illustrated in FIGS. 16A-16C, and generallyresembles the graft 510, e.g., including a pair of graft subassemblies312 a and 312 b (collectively, the “subassemblies 312”) connectedtogether by a conduit section 51. Unlike the graft 510, in which both ofthe subassemblies 302 resemble the bifurcated graft 110 of FIG. 1B, thesubassembly 312 b of the graft 610 is a straight graft subassembly thatgenerally resembles the straight vascular graft 10 of FIG. 1A, while thesubassembly 312 a is a bifurcated graft subassembly resembling the graft110. It is noted that due to the lack of bifurcation of the subassembly312 b in this embodiment, blood flowing through the vessel portion 306 bmay be blocked or impeded by the subassembly 312 b. That is, all or mostof the blood flow that is flowing through the vessel portion 306 b inthe direction of the subassembly 312 a from the subassembly 312 b willbe diverted through the conduit section 51 instead of continuing throughthe vessel portion 306 b. Thus, the graft 610 is particularlyadvantageous in embodiments in which blood flow through the vesselportion 306 b on both sides of the subassembly 312 b is not necessary,e.g., such as when the vessel portions 306 are part of the same vessel,and an occlusion is present therebetween, and thus a bypass of thatocclusion is desired.

A vascular graft 710 is illustrated in FIGS. 17A-17C, and generallyresembles the grafts 510 and/or 610, e.g., including a pair of graftsubassemblies 322 a and 322 b (collectively, the “subassemblies 322”)connected together by a conduit section 51. Similar to the subassembly312 b of the graft 610, both of the subassemblies 322 are straight graftsubassemblies, resembling the graft 10 without bifurcations. For thisreason, and similar to the subassembly 312 b, both of the subassemblies322 may block or impede blood flow through the respective vessel portion306 in which they are inserted. Thus, the graft 710 may accordingly beparticularly useful in embodiments in which an occlusion is presentbetween the vessel portions 306, and thus a bypass of that occlusion isdesired.

It is to be appreciated that the subassemblies 510, 610, and 710 mayinclude tapered, trumpeted, or flared inflow and/or outflow regions,according to the above descriptions thereof. That is, the supportstructures 40 in the subassemblies 510, 610, and/or 710 may be arrangedand constructed of nitinol or other shape memory material, or otherwisebe configured to naturally transition to a radially expanded shape.Additionally, the support structure 40 may, similar to the abovedisclosure herein, be further radially expanded by use of an inflatableballoon 97 or other device inserted within the support structure 40.

Numerous modifications and alternative embodiments of the presentinvention will be apparent to those skilled in the art in view of theforegoing description. Accordingly, this description is to be construedas illustrative only and is for the purpose of teaching those skilled inthe art the best mode for carrying out the present invention. Details ofthe structure may vary substantially without departing from the spiritof the present invention, and exclusive use of all modifications thatcome within the scope of the appended claims is reserved. Within thisspecification embodiments have been described in a way which enables aclear and concise specification to be written, but it is intended andwill be appreciated that embodiments may be variously combined orseparated without parting from the invention. It is intended that thepresent invention be limited only to the extent required by the appendedclaims and the applicable rules of law.

It is also to be understood that the following claims are to cover allgeneric and specific features of the invention described herein, and allstatements of the scope of the invention which, as a matter of language,might be said to fall therebetween.

1-52. (canceled)
 53. A graft, comprising: a conduit having a wall, theconduit comprising: a first inflow region having a first inflow end anda second inflow region having a second inflow end, the first and secondinflow regions merging together at an inflow junction, which is in fluidcommunication with an elongate expandable outflow region opposite thefirst inflow region, the outflow region having an outflow end; a firstinflow aperture disposed at the first inflow end of the first inflowregion, a second inflow aperture disposed at the second inflow end ofthe second inflow region, and an outflow aperture disposed at theoutflow end of the outflow region; wherein the wall comprises a supportstructure and a biocompatible layer; wherein the support structure alongat least a portion of the elongate expandable outflow region is undercompressive stress resulting from an applied load caused by thebiocompatible layer against the support structure; and wherein thelength of the elongate expandable outflow region is greater than twicethe length of either the first inflow region or the second inflowregion.
 54. The graft of claim 53, wherein the elongate expandableoutflow region has a length greater than the length of either the firstinflow region or the second inflow region.
 55. The graft of claim 53,wherein the length of the conduit between the inflow junction and theoutflow end is at least about 100 millimeters.
 56. The graft of claim53, wherein the compressive stress resulting from the continuous appliedload in the elongate expandable outflow region is greater than acompressive stress resulting from a continuous applied load in eitherthe first inflow region or the second inflow region.
 57. The graft ofclaim 53, wherein the compressive stress experienced by the supportstructure resulting from the continuous applied load in the elongateexpandable outflow region incrementally increases at one or more initialsegments along the support structure before becoming substantiallyconstant across each segment that is incrementally more distal from theone or more initial segments.
 58. The graft of claim 53, wherein thecompressive stress experienced by the support structure resulting fromthe continuous applied load in the elongate expandable outflow regioncauses an elastic deformation of the support structure in the elongateexpandable outflow region.
 59. The graft of claim 58, wherein theelastic deformation of the support structure in the outflow regionincreases at one or more initial segments along the support structurebefore becoming substantially constant across each segment that isincrementally more distal from the one or more initial segments.
 60. Thegraft of claim 58, wherein the elastic deformation of the supportstructure in the elongate expandable outflow region is reversible. 61.The graft of claim 53, wherein reversing the elastic deformation of thesupport structure in the elongate expandable outflow region expands thediameter of the support structure in the elongate expandable outflowregion to a diameter that is greater than the uncompressed diameter ofthe support structure not under compressive stress resulting from thecontinuous applied load in the elongate expandable outflow region.62-63. (canceled)
 64. The graft of claim 53, wherein the supportstructure prior to combination with the biocompatible layer to form thewall has multiple effective inner diameter measurements, and the supportstructure after combination with the biocompatible layer to form thewall has a generally uniform effective inner diameter measurement.65-77. (canceled)
 78. The graft of claim 53, wherein a longitudinal axisof the second inflow region intersects a longitudinal axis of the firstinflow region at a non-parallel angle.
 79. The graft of claim 78,wherein the non-parallel angle comprises an angle between about 25° and45°.
 80. The graft of claim 78, wherein the non-parallel angle comprisesan angle of about 35°.
 81. The graft of claim 78, wherein the secondinflow region merges together at the inflow junction with the firstinflow region in such a way that the first inflow region and the secondinflow region are not perpendicular to each other.
 82. The graft ofclaim 53, wherein the support structure is constructed of a shape memoryalloy.
 83. The graft of claim 53, wherein the support structure isconstructed of nitinol.
 84. The graft of claim 53, wherein thebiocompatible layer comprises an expandable polymer.
 85. The graft ofclaim 53, wherein the biocompatible layer comprises ePTFE.
 86. The graftof claim 53, wherein the biocompatible layer further comprises abiocompatible outer layer.
 87. The graft of claim 86, wherein thebiocompatible layer further comprises a biocompatible inner layer.88-225. (canceled)